Arynes, or dehydrobenzenes, are aromatic compounds with a formal triple bond between two adjacent carbons. The simplest example is benzyne itself, C6H4. Arynes constitute one of the main classes of reactive intermediates whose methods of generation and synthetic utility in organic chemistry is well established. In contrast, di-arynes, compounds with two such reactive sites, are virtually unknown. We propose to synthesize compounds which are the synthetic equivalent of di-arynes, and demonstrate their versatility in the rapid build-up of complex, multi-ring structures with potential pharmacologic activity. Cycloaddition reactions of di-aryne equivalents with dienes, 1,3-dipoles and electron-rich alkenes will be developed. These reactions will result in the simultaneous fusion of two new rings to an existing aromatic ring. The new rings will be, respectively, six-, five- or four-membered, and they may be carbocyclic or heterocyclic. Dienes, for example, will in this way give linearly fused six-membered rings similar to the arrangement in anthracyclines. 1,3-Dipoles will lead to new heterocyclic systems whose pharmacologic activity will be tested. And electron-rich alkenes will lead to useful benzodicyclobutene synthons. Factors which affect the regio-and/or stereo-selectivity will be studied. Certain di-aryne adducts are anticipated to be useful precursors of polyfunctional macrocycles or ditropones or polyepoxides. These possibilities and the potential antiviral, antibiotic and anticancer activity of these polyfunctional molecules will be tested. New di-aryne precursors for polynuclear aromatic hydrocarbon synthesis will be developed. A new route to unsymmetric biaryls and terphenyls will be developed. In a second research area, the cycloaddition of cyclic dienones to nitroso compounds, the 1,4-cycloaddition of carbenes to cyclopentadienones, the photochemical isomerization of dienone-carbene adducts and the chemistry of di-aryne-dienone cycloadducts will be studied as routes to novel polyfunctional molecules with potential pharmacologic activity. The long-term goal of this research is to develop new synthetic routes to novel organic molecules with potential biological activity.